2006 Fiscal Year Final Research Report Summary
Functional analysis of neuroprotective factor Humanin as a basis for Alzheimer's disease therapy
| Project/Area Number |
17590894
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Keio University |
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Principal Investigator |
NIIKURA Takako Keio University, School of Medicine, Instructor (10301491)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Alzheimer's disease / Humanin / neuronal death / neuronrotective factor / peptide / peptide derivative / amyloid beta |
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| Research Abstract |
In Alzheimer's disease (AD), prevention of neuronal cell death should slow down the disease progression. Humanin (HN) is a 24-residue neuroprotective peptide (MAPRGFSCLLLLTSEIDLPVKRRA). In vitro studies showed that HN protected neurons from various types of AD-related insults, which include amyloid beta peptides and familial AD-linked mutants of amyloid precursor protein and presenilins. Amino acid replacement study revealed that the substitution of Ser14 to Gly (S14G-HN) drastically increased its action potency in vitro neuroprotection assays: S14G-HN is effective at 1-10nM of concentration whereas HN protects neurons at 1-10mM. Furthermore, S14G-HN ameliorated memory deficit induced by amylid beta by intracerebroventricular injection, while HN showed the same tendency that was not statistically significant. To elucidate action mechanism of HN and S14G-HN, we performed secondary structure analysis by circular dichroism. The secondary structure of these peptides was significantly different in phosphate-buffered saline. The structural change of S14G-HN was observed in a concentration and temperature-dependent manner, suggesting self-association via hydrophobic interaction.
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Author(s)
Du W, Hattori Y, Yamada T, Matsumoto K, Nakamura T, Sagawa M, Otsuki T, Niikura T, et. al.
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Journal Title
Blood 109
Pages: 3042-3049
Description
「研究成果報告書概要(和文)」より
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[Journal Article] NK4, an antagonist of hepatocyte growth factor(HGF), inhibits growth of multiple myeloma cells in vivo ; molecular targeting of angiogenic growth factor2007
Author(s)
Du W, Hattori Y, Yamada T, Matsumoto K, Nakamura T, Sagawa M, Otsuki T, Niikura T, Nukiwa T, Ikeda Y.
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Journal Title
Blood 109
Pages: 3042-3049
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Expression of N19S-SOD1, a SOD1 mutant found in sporadic amyotrophic lateral sclerosis(ALS) patients, induces low-grade motoneuronal toxicity.2005
Author(s)
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Journal Title
J. Neurosci. Res. 81
Pages: 720-729
Description
「研究成果報告書概要(欧文)」より
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